A patient taking fexofenadine for allergic rhinitis drinks large quantities of grapefruit juice daily and reports poor symptom control. The pharmacokinetic explanation is:

• A Grapefruit juice induces CYP3A4 and accelerates hepatic clearance of fexofenadine
• B Grapefruit juice inhibits intestinal CYP3A4 and increases fexofenadine toxicity
• C Grapefruit juice blocks the OATP uptake transporter and reduces fexofenadine absorption ✓
• D Grapefruit juice displaces fexofenadine from plasma protein binding sites

Explanation

Fexofenadine is unusual among second-generation antihistamines because it undergoes minimal CYP450 metabolism and is instead transported across the gut wall by organic anion transporting polypeptide (OATP1A2) and P-glycoprotein. Components of grapefruit juice inhibit OATP-mediated uptake, reducing bioavailability and lowering plasma concentrations, so efficacy falls. This is opposite to the classic grapefruit juice interaction with midazolam or statins, where CYP3A4 inhibition raises drug levels. Protein binding displacement is clinically insignificant here.

Reference: Katzung's Basic and Clinical Pharmacology, 15th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.